Objective:To investigate the effects of electroacupuncture (EA) at acupoints Baihui (GV 20), Neiguan (PC 6) and Sanyinjiao (SP 6) on the levels of estradiol (E2) and brain-derived neurotrophic factor (BDNF) in serum, as well as the expression of BDNF in hippocampus in chronic depression rat models. Methods:Thirty female Wistar rats were randomly divided into three groups, including a normal control (NC) group, a model group and an EA group, 10 rats in each group. The depression model was established by using chronic unpredicted mild stress (CUMS), such as cold-water swimming, tail clamping, electric shock to foot, etc., combined with individual caging for 21 d. Rats in the model group and EA group were randomly exposed to one of the 9 stressors each day and caged individually. After modeling, rats in the EA group were then treated with EA at Baihui (GV 20), Neiguan (PC 6) and Sanyinjiao (SP 6) once daily for 14 d, and the model group was not treated with EA but bounded in the same way as the EA group. Serum E2 was measured by radioimmunoassay and BDNF was assessed by an enzyme-linked immunosorbent assay (ELISA) and the expression of BDNF in hippocampus was detected by using immunohistochemistry. Results:After the stress stimulation, compared with the NC group, the model group and EA group showed a significant reduction of sucrose preference rate (P<0.01) and remarkable increase of forced-swimming immobility time (P<0.01). In addition, EA significantly reduced the depression-like behavior of rats in the EA group (P<0.01). The expressions of E2 and BDNF in serum as well as the expression of BDNF in hippocampus were remarkably lower in the model rats than those in the NC group (P<0.01,P<0.01,P<0.05). The expression of BDNF in rats’ serum and hippocampus in the EA group was significantly higher than that in the model group (P<0.05), while serum E2 increased but insignificantly (P>0.05). Conclusion:E2 and BDNF may contribute to the depression-like behaviors of the rats during CUMS period. EA may exert its anti-depression effects through promoting BDNF expression in serum and hippocampus.